Non Muscle Invasive Bladder CancerHIVECNCT07231809
Hyperthermic Intravesical Chemotherapy (HIVEC) in BCG-Non-Responsive High-Grade NMIBC Patients
A study testing Hyperthermic Intravesical Chemotherapy (HIVEC) in people with Non Muscle Invasive Bladder Cancer and Bladder Cancer, run by AC.TA. S.r.l. at 1 site in Italy.
Trial summary
This is a Phase II, prospective, single-arm, open-label clinical study evaluating hyperthermic intravesical chemotherapy (HIVEC) with Mitomycin C in patients with high-grade, non-muscle-invasive bladder cancer (NMIBC) who are BCG-non-responsive or BCG-intolerant and are ineligible for, or refuse, radical cystectomy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Muscle Invasive Bladder Cancer, Bladder Cancer, Carcinoma in Situ of Bladder
- What is being tested?
- Hyperthermic Intravesical Chemotherapy (HIVEC)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteItaly
- Study dates
- 15 Oct 2026to 31 May 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years.
- Histologically confirmed high-grade non-muscle-invasive bladder cancer (NMIBC), including Ta, T1, and/or carcinoma in situ (CIS).
- BCG-unresponsive or BCG-intolerant disease according to international definitions (persistent or recurrent high-grade NMIBC after adequate BCG therapy).
- Patient is ineligible for, or refuses, radical cystectomy.
- Candidate for hyperthermic intravesical chemotherapy (HIVEC) according to clinical judgment.
- ECOG Performance Status 0-2.
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- Adequate organ function according to institutional standards.
- Ability and willingness to comply with study procedures and follow-up schedule.
- Written informed consent obtained.
Who cannot join
- Muscle-invasive bladder cancer (≥ T2) or metastatic disease.
- Active urinary tract infection at baseline.
- Previous treatment with HIVEC or other intravesical hyperthermia systems.
- Known hypersensitivity to Mitomycin C or contraindications to intravesical chemotherapy.
- Active uncontrolled bleeding or gross hematuria preventing intravesical instillation.
- Upper urinary tract urothelial carcinoma.
- Pregnant or breastfeeding women.
- Any medical or psychological condition that, in the investigator's judgment, could interfere with study participation or compromise patient safety.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site
P.O. "Santa Maria delle Grazie" - ASL Napoli 2 Nord
Pozzuoli, 80078
Gaetano Facchini, MD, +3908118844043, gaetano.facchini@aslnapoli2nord.it
Gaetano Facchini, MD
About this study
Official title: Hyperthermic Intravesical Chemotherapy (HIVEC) In Patients With BCG-Non Responsive Or Intolerant High-Grade BCG-Infiltrating Non-Muscle-Infiltrating Bladder Cancer And Not Eligible For Radical Cystectomy: Phase II Study (SMG-Bladder 01).
This is a Phase II, prospective, single-arm, open-label clinical study evaluating hyperthermic intravesical chemotherapy (HIVEC) with Mitomycin C in patients with high-grade, non-muscle-invasive bladder cancer (NMIBC) who are BCG-non-responsive or BCG-intolerant and are ineligible for, or refuse, radical cystectomy. Mitomycin C is an approved medicinal product used within routine clinical practice and administered with a CE-marked recirculation device (BRS Combat system) that maintains the solution at approximately 43°C for 60 minutes. The treatment schedule consists of 6 weekly induction instillations followed by 9 monthly maintenance instillations.
The co-primary objectives are to describe the safety and toxicity profile of HIVEC, including treatment discontinuations due to procedure-related toxicity, and to estimate the 12-month recurrence-free survival (12moRFS). Secondary objectives include characterizing patterns of non-muscle-invasive and muscle-invasive recurrences, bladder cancer-specific survival, overall survival, and quality of life. Approximately 50 patients will be enrolled in this single-center pilot study to generate exploratory safety and efficacy data in this high-risk population and to support the design of future randomized trials
Read the detailed description
This is an interventional, prospective, single-center, single-arm, open-label, Phase II study conducted in patients with high-grade non-muscle-invasive urothelial carcinoma of the bladder (NMIBC) who are BCG-non-responsive or BCG-intolerant according to European Association of Urology criteria, and who are either not eligible for, or decline, radical cystectomy. Radical cystectomy remains the standard of care in this setting, but many patients are unfit because of age or comorbidities or are unwilling to undergo major surgery. Hyperthermic intravesical chemotherapy (HIVEC) has emerged as a potential alternative option for disease control in these high-risk patients. 
In this study, Mitomycin C 80 mg in 80 mL of sterile water is administered intravesically using the CE-marked BRS Combat recirculation system, which keeps the solution at a controlled temperature of about 43°C for 60 minutes. The treatment regimen includes an induction phase of 6 weekly instillations followed by a maintenance phase of 9 monthly instillations. Therapy may be discontinued earlier in the event of disease progression or unacceptable toxicity. Mitomycin C is purchased by the ASL Napoli 2 Nord as part of routine care, with costs reimbursed by the sponsor, while the device and related disposables are supplied on loan for use for the study. 
The co-primary endpoints are: (1) toxicity and safety, including the type, incidence, severity, and timing of adverse events graded according to NCI CTCAE v5.0 and PRO-CTCAE, and the proportion of patients who discontinue treatment due to procedure-related toxicity; and (2) 12-month recurrence-free survival (12moRFS), defined as the time from first instillation to recurrence or progression (Ta, T1, or CIS) or death from any cause, with estimates obtained using the Kaplan-Meier method. Secondary endpoints include the rate of Ta-T1 non-muscle-invasive recurrences, the proportion of muscle-invasive recurrences (≥T2), bladder cancer-specific survival, overall survival, and quality of life assessed with the EORTC QLQ-NMIBC24 questionnaire at predefined time points during treatment and follow-up. 
Approximately 50 patients will be enrolled between November 2025 and November 2026 at the Oncology and Urology Units of the "S. Maria delle Grazie" Hospital in Pozzuoli (ASL Napoli 2 Nord). Data will be recorded in an electronic database using anonymized patient codes. Statistical analyses will be primarily descriptive and exploratory, reflecting the monocentric, non-comparative design and the pilot nature of the study, with the aim of characterizing the safety profile of HIVEC and providing a preliminary estimate of 12-month recurrence-free survival and overall disease control in this population.
- Conditions
- Non Muscle Invasive Bladder Cancer, Bladder Cancer, Carcinoma in Situ of Bladder, Urinary Bladder Neoplasms, Carcinoma, Transitional Cell, Bladder
- Being tested
- Hyperthermic Intravesical Chemotherapy (HIVEC)
- Keywords
- HIVEC, Hyperthermic Intravesical Chemotherapy, Mitomycin C, BRS Combat System, Bladder Tumor Recurrence, High-Grade Bladder Cancer
- Medical subject headings
- Non-Muscle Invasive Bladder Neoplasms, Urinary Bladder Neoplasms, Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hyperthermic Intravesical Chemotherapy (HIVEC)Procedure or surgery
Also called HIVEC System, BRS Combat
Intravesical administration of Mitomycin C heated to approximately 43°C using a CE-marked recirculation system (BRS Combat device). Mitomycin C is supplied by the treating hospital as part of routine clinical practice. The procedure consists of 6 weekly instillations followed by 9 monthly instillations.
| Study group | Role | What they receive |
|---|---|---|
| HIVEC Treatment Arm | Experimental | Participants will receive Hyperthermic Intravesical Chemotherapy (HIVEC) with Mitomycin C according to the study protocol (induction + maintenance schedule). Mitomycin C is an approved medicinal product used within routine clinical practice. HIVEC is performed using a CE-marked recirculation system that maintains the solution at a controlled therapeutic temperature. Receives: Procedure: Hyperthermic Intravesical Chemotherapy (HIVEC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment-Related Adverse Events (AEs)
Incidence, type, timing, and severity of adverse events graded according to NCI CTCAE v5.0. Includes local and systemic toxicities related to hyperthermic intravesical chemotherapy and the proportion of patients who discontinue treatment due to toxicity.
Measured: Up to 12 months
12-Month Recurrence-Free Survival (RFS)
Proportion of patients who remain free from histologically confirmed recurrence of non-muscle-invasive bladder cancer (Ta, T1, or CIS) at 12 months from initiation of HIVEC treatment. Recurrence is defined per standard cystoscopic and histological criteria.
Measured: 12 months after completion of the HIVEC treatment schedule
Secondary outcomes (5)
Rate of non-muscle-invasive (Ta-T1) bladder cancer recurrences
Percentage of patients experiencing a histologically confirmed Ta or T1 recurrence during the 12-month follow-up period.
Measured: Up to 12 months
Rate of muscle-invasive (≥T2) recurrences
Percentage of patients who progress to muscle-invasive bladder cancer (≥T2) confirmed by imaging or histology.
Measured: Up to 12 months
Cancer-specific survival
Assessing cancer-specific survival (bladder)
Measured: up to 12 months
Overall Survival (OS)
Time from first HIVEC instillation to death from any cause.
Measured: Up to 12 months
Quality of Life (QoL)
Quality of life will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Non-Muscle-Invasive Bladder Cancer Module (EORTC QLQ-NMIBC24).
The questionnaire generates multi-item symptom and function scales scored from 0 to 100, where higher scores indicate worse symptoms or lower functioning in accordance with the official EORTC scoring manual
Measured: Up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2025
- Study start15 Oct 2026 (estimated)
- Primary completion31 May 2028 (estimated)
- Study completion31 May 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non Muscle Invasive Bladder CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Prospective, single-arm, non-randomized, Phase II therapeutic study evaluating hyperthermic intravesical chemotherapy.
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AC.TA. S.r.l.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gaetano Facchini, MD, Principal investigator, P.O. "Santa Maria delle Grazie" - ASL Napoli 2 Nord
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07231809
- Sponsor's protocol ID
- SMG-Bladder 01
- Acronym
- HIVEC
- Status last verified
- May 2026
- First submitted
- 14 Nov 2025
- Last updated
- 6 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: The decision regarding IPD sharing is not finalized. Potential data sharing will depend on institutional policies, GDPR requirements, and Ethics Committee approval. Any sharing would involve only de-identified data and would require a formal data sharing agreement.
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hyperthermic Intravesical Chemotherapy (HIVEC) In Patients With BCG-Non Responsive Or Intolerant High-Grade BCG-Infiltrating Non-Muscle-Infiltrating Bladder Cancer And Not Eligible For Radical Cystectomy: Phase II Study (SMG-Bladder 01).
- ClinicalTrials.gov ID
- NCT07231809
- Acronym / sponsor ID
- HIVEC / SMG-Bladder 01
- Conditions
- Non Muscle Invasive Bladder Cancer, Bladder Cancer, Carcinoma in Situ of Bladder, Urinary Bladder Neoplasms, Carcinoma, Transitional Cell, Bladder
- Keywords
- HIVEC, Hyperthermic Intravesical Chemotherapy, Mitomycin C, BRS Combat System, Bladder Tumor Recurrence, High-Grade Bladder Cancer
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- AC.TA. S.r.l.Industry (pharma, biotech, devices)
- Study start
- 15 Oct 2026 (estimated)
- Primary completion
- 31 May 2028 (estimated)
- Study completion
- 31 May 2028 (estimated)
- First posted
- 17 Nov 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase II, prospective, single-arm, open-label clinical study evaluating hyperthermic intravesical chemotherapy (HIVEC) with Mitomycin C in patients with high-grade, non-muscle-invasive bladder cancer (NMIBC) who are BCG-non-responsive or BCG-intolerant and are ineligible for, or refuse, radical cystectomy. Mitomycin C is an approved medicinal product used within routine clinical practice and administered with a CE-marked recirculation device (BRS Combat system) that maintains the solution at approximately 43°C for 60 minutes. The treatment schedule consists of 6 weekly induction instillations followed by 9 monthly maintenance instillations.
The co-primary objectives are to describe the safety and toxicity profile of HIVEC, including treatment discontinuations due to procedure-related toxicity, and to estimate the 12-month recurrence-free survival (12moRFS). Secondary objectives include characterizing patterns of non-muscle-invasive and muscle-invasive recurrences, bladder cancer-specific survival, overall survival, and quality of life. Approximately 50 patients will be enrolled in this single-center pilot study to generate exploratory safety and efficacy data in this high-risk population and to support the design of future randomized trials
Detailed description
This is an interventional, prospective, single-center, single-arm, open-label, Phase II study conducted in patients with high-grade non-muscle-invasive urothelial carcinoma of the bladder (NMIBC) who are BCG-non-responsive or BCG-intolerant according to European Association of Urology criteria, and who are either not eligible for, or decline, radical cystectomy. Radical cystectomy remains the standard of care in this setting, but many patients are unfit because of age or comorbidities or are unwilling to undergo major surgery. Hyperthermic intravesical chemotherapy (HIVEC) has emerged as a potential alternative option for disease control in these high-risk patients. 
In this study, Mitomycin C 80 mg in 80 mL of sterile water is administered intravesically using the CE-marked BRS Combat recirculation system, which keeps the solution at a controlled temperature of about 43°C for 60 minutes. The treatment regimen includes an induction phase of 6 weekly instillations followed by a maintenance phase of 9 monthly instillations. Therapy may be discontinued earlier in the event of disease progression or unacceptable toxicity. Mitomycin C is purchased by the ASL Napoli 2 Nord as part of routine care, with costs reimbursed by the sponsor, while the device and related disposables are supplied on loan for use for the study. 
The co-primary endpoints are: (1) toxicity and safety, including the type, incidence, severity, and timing of adverse events graded according to NCI CTCAE v5.0 and PRO-CTCAE, and the proportion of patients who discontinue treatment due to procedure-related toxicity; and (2) 12-month recurrence-free survival (12moRFS), defined as the time from first instillation to recurrence or progression (Ta, T1, or CIS) or death from any cause, with estimates obtained using the Kaplan-Meier method. Secondary endpoints include the rate of Ta-T1 non-muscle-invasive recurrences, the proportion of muscle-invasive recurrences (≥T2), bladder cancer-specific survival, overall survival, and quality of life assessed with the EORTC QLQ-NMIBC24 questionnaire at predefined time points during treatment and follow-up. 
Approximately 50 patients will be enrolled between November 2025 and November 2026 at the Oncology and Urology Units of the "S. Maria delle Grazie" Hospital in Pozzuoli (ASL Napoli 2 Nord). Data will be recorded in an electronic database using anonymized patient codes. Statistical analyses will be primarily descriptive and exploratory, reflecting the monocentric, non-comparative design and the pilot nature of the study, with the aim of characterizing the safety profile of HIVEC and providing a preliminary estimate of 12-month recurrence-free survival and overall disease control in this population.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Prospective, single-arm, non-randomized, Phase II therapeutic study evaluating hyperthermic intravesical chemotherapy.
| Arm | Type | Receives |
|---|---|---|
| HIVEC Treatment Arm | Experimental | Procedure: Hyperthermic Intravesical Chemotherapy (HIVEC)Participants will receive Hyperthermic Intravesical Chemotherapy (HIVEC) with Mitomycin C according to the study protocol (induction + maintenance schedule). Mitomycin C is an approved medicinal product used within routine clinical practice. HIVEC is performed using a CE-marked recirculation system that maintains the solution at a controlled therapeutic temperature. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age ≥ 18 years.
- Histologically confirmed high-grade non-muscle-invasive bladder cancer (NMIBC), including Ta, T1, and/or carcinoma in situ (CIS).
- BCG-unresponsive or BCG-intolerant disease according to international definitions (persistent or recurrent high-grade NMIBC after adequate BCG therapy).
- Patient is ineligible for, or refuses, radical cystectomy.
- Candidate for hyperthermic intravesical chemotherapy (HIVEC) according to clinical judgment.
Key exclusion criteria (8 listed)
- Muscle-invasive bladder cancer (≥ T2) or metastatic disease.
- Active urinary tract infection at baseline.
- Previous treatment with HIVEC or other intravesical hyperthermia systems.
- Known hypersensitivity to Mitomycin C or contraindications to intravesical chemotherapy.
- Active uncontrolled bleeding or gross hematuria preventing intravesical instillation.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hyperthermic Intravesical Chemotherapy (HIVEC)Also: HIVEC System, BRS CombatIntravesical administration of Mitomycin C heated to approximately 43°C using a CE-marked recirculation system (BRS Combat device). Mitomycin C is supplied by the treating hospital as part of routine clinical practice. The procedure consists of 6 weekly instillations followed by 9 monthly instillations. | Procedure or surgery | HIVEC Treatment Arm |
Primary outcome
Treatment-Related Adverse Events (AEs)
Time frame: Up to 12 months
Incidence, type, timing, and severity of adverse events graded according to NCI CTCAE v5.0. Includes local and systemic toxicities related to hyperthermic intravesical chemotherapy and the proportion of patients who discontinue treatment due to toxicity.
12-Month Recurrence-Free Survival (RFS)
Time frame: 12 months after completion of the HIVEC treatment schedule
Proportion of patients who remain free from histologically confirmed recurrence of non-muscle-invasive bladder cancer (Ta, T1, or CIS) at 12 months from initiation of HIVEC treatment. Recurrence is defined per standard cystoscopic and histological criteria.
5 secondary outcomes
Rate of non-muscle-invasive (Ta-T1) bladder cancer recurrences
Time frame: Up to 12 months
Rate of muscle-invasive (≥T2) recurrences
Time frame: Up to 12 months
Cancer-specific survival
Time frame: up to 12 months
Overall Survival (OS)
Time frame: Up to 12 months
Quality of Life (QoL)
Time frame: Up to 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2026.
- Individual participant dataSharing planned: Undecided. The decision regarding IPD sharing is not finalized. Potential data sharing will depend on institutional policies, GDPR requirements, and Ethics Committee approval. Any sharing would involve only de-identified data and would require a formal data sharing agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Gaetano Facchini, MD principal investigator
P.O. "Santa Maria delle Grazie" - ASL Napoli 2 Nord
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Hyperthermic Intravesical Chemotherapy (HIVEC) in people with Non Muscle Invasive Bladder Cancer and Bladder Cancer, run by AC.TA. S.r.l. at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 6 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Gaetano Facchini, MD (+3908118844043, gaetano.facchini@aslnapoli2nord.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment-Related Adverse Events (AEs) (time frame: Up to 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2026.